Discriminating Epithelial to Mesenchymal Transition Phenotypes in Circulating Tumor Cells Isolated from Advanced Gastrointestinal Cancer Patients

Cells

Lúcio Lara Santos¹  Luís Lima¹  Dylan Ferreira¹  Sofia Cotton¹  Paulina Piairo²  Alexandra Teixeira²  Adriana Carneiro²  Lorena Diéguez²  Sara Abalde-Cela²  Carolina Rodrigues²  Alexandre Chícharo² 

[1] IPO Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal;International Iberian Nanotechnology Laboratory, Avenida Mestre José Veiga s/n, 4715-330 Braga, Portugal;

关键词: circulating tumor cells;    gastrointestinal cancer;    epithelial-to-mesenchymal transition;    metastasis;    liquid biopsy;    microfluidics;   

DOI  :  10.3390/cells11030376

来源: DOAJ

【 摘 要 】

Gastrointestinal (GI) cancers constitute a group of highest morbidity worldwide, with colorectal cancer (CRC) and gastric cancer being among the most frequently diagnosed. The majority of gastrointestinal cancer patients already present metastasis by the time of diagnosis, which is widely associated with cancer-related death. Accumulating evidence suggests that epithelial-to-mesenchymal transition (EMT) in cancer promotes circulating tumor cell (CTCs) formation, which ultimately drives metastasis development. These cells have emerged as a fundamental tool for cancer diagnosis and monitoring, as they reflect tumor heterogeneity and the clonal evolution of cancer in real-time. In particular, EMT phenotypes are commonly associated with therapy resistance. Thus, capturing these CTCs is expected to reveal important clinical information. However, currently available CTC isolation approaches are suboptimal and are often targeted to capture epithelial CTCs, leading to the loss of EMT or mesenchymal CTCs. Here, we describe size-based CTCs isolation using the RUBYchip™, a label-free microfluidic device, aiming to detect EMT biomarkers in CTCs from whole blood samples of GI cancer patients. We found that, for most cases, the mesenchymal phenotype was predominant, and in fact a considerable fraction of isolated CTCs did not express epithelial markers. The RUBYchip™ can overcome the limitations of label-dependent technologies and improve the identification of CTC subpopulations that may be related to different clinical outcomes.

【 授权许可】

Unknown